Comparison of systemic and mucosal delivery of 2 canarypox virus vaccines expressing either HIV-1 genes or the gene for rabies virus G protein

被引:45
作者
Wright, PF
Mestecky, J
McElrath, MJ
Keefer, MC
Gorse, GJ
Goepfert, PA
Moldoveanu, Z
Schwartz, D
Spearman, PW
El Habib, R
Spring, MD
Zhu, YW
Smith, C
Flores, J
Weinhold, KJ
机构
[1] Vanderbilt Univ, Med Ctr, Sch Med, Dept Pediat,Sect Infect Dis, Nashville, TN 37232 USA
[2] Univ Alabama, Dept Med, Mucosal Immunol Lab, Birmingham, AL USA
[3] Univ Washington, Sch Med, Seattle, WA USA
[4] Univ Rochester, Sch Med & Dent, Rochester, NY USA
[5] St Louis Dept Vet Affairs Med Ctr, St Louis, MO USA
[6] St Louis Univ, Sch Med, St Louis, MO USA
[7] Johns Hopkins Univ, Sch Med, Baltimore, MD USA
[8] EMMES Corp, Rockville, MD USA
[9] NIAID, Div AIDS, Bethesda, MD USA
[10] Duke Univ, Med Ctr, Cent Immunol Lab, Durham, NC USA
[11] Pasteur Aventis, Marcy Letoile, France
关键词
D O I
10.1086/382088
中图分类号
R392 [医学免疫学]; Q939.91 [免疫学];
学科分类号
100102 ;
摘要
Background. Since the primary routes of human immunodeficiency type 1 (HIV-1) infection are across mucosal barriers, a randomized trial of canarypox virus - based vectors was conducted in 84 individuals, with delivery of vaccine by mucosal routes, and was accompanied by a detailed analysis of humoral, cellular, and mucosal immune responses. Methods. Over the course of 6 months, HIV-1 - specific (vCP 205) and rabies ( vCP 65) canarypox virus vectors were delivered systemically and/or mucosally into the nose, mouth, vagina, or rectum in a 4-dose schedule, followed by 2 doses of HIV-1 MN recombinant glycoprotein (rgp) 120 or subunit rabies vaccine administered by the intramuscular route. Results. Administration of vaccine and collection of samples were well tolerated. Serum IgG HIV-1 - specific antibodies to rgp120 were rarely seen after either systemic or mucosal delivery of canarypox virus vaccine. In contrast, serum IgG rabies and canarypox antibodies were detected in all individuals after systemic, but rarely after mucosal, delivery of vaccine. Suggestions of mucosal recognition of HIV-1 antigen included a cytotoxic T lymphocyte response in 4 of 8 individuals after administration of vaccine by the intrarectal route and a limited immunoglobulin A response at the same site. Conclusions. Each of the routes of vaccine administration was feasible in the context of a phase 1 study with motivated individuals. However, with the doses and routes of administration used, canarypox virus was not an effective mucosal immunogen.
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页码:1221 / 1231
页数:11
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